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BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma
Laubscher et. al.
Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters...

A Tumor Suppressor Enhancer of PTEN in T-cell development and leukemia
L. Tottone at al.
Long-range oncogenic enhancers play an important role in cancer. Yet, whether similar regulation of tumor suppressor genes is relevant remains unclear. Loss of expression of PTEN is associated with the pathogenesis of various cancers, including T-cell leukemia (T-ALL). Here, we identify a highly conserved distal enh...

Genomic profiling of T-cell activation suggests increased sensitivity ofmemory T cells to CD28 costimulation.
Glinos, Dafni A and Soskic, Blagoje and Williams, Cayman and Kennedy, Alanand Jostins, Luke and Sansom, David M and Trynka, Gosia
T-cell activation is a critical driver of immune responses. The CD28 costimulation is an essential regulator of CD4 T-cell responses, however, its relative importance in naive and memory T cells is not fully understood. Using different model systems, we observe that human memory T cells are more sensitive to CD28 co...

A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.
Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain
Interferon β (IFN-β) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previous...

BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.
Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunit...

Macrophage Immune Memory Controls Endometriosis in Mice and Humans.
Jeljeli, Mohamed and Riccio, Luiza G C and Chouzenoux, Sandrine and Moresi,Fabiana and Toullec, Laurie and Doridot, Ludivine and Nicco, Carole andBourdon, Mathilde and Marcellin, Louis and Santulli, Pietro and Abrão,Mauricio S and Chapron, Charles and
Endometriosis is a frequent, chronic, inflammatory gynecological disease characterized by the presence of ectopic endometrial tissue causing pain and infertility. Macrophages have a central role in lesion establishment and maintenance by driving chronic inflammation and tissue remodeling. Macrophages can be reprogra...

UTX/KDM6A suppresses AP-1 and a gliogenesis program during neuraldifferentiation of human pluripotent stem cells.
Xu, Beisi and Mulvey, Brett and Salie, Muneeb and Yang, Xiaoyang andMatsui, Yurika and Nityanandam, Anjana and Fan, Yiping and Peng, Jamy C
BACKGROUND: UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear. RESULTS: We report that in human neural stem cells, UTX binding correla...

Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.
Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael
Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vasc...

Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.
Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM
Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetyla...

Methylation in pericytes after acute injury promotes chronic kidneydisease.
Chou, YH and Pan, SY and Shao, YH and Shih, HM and Wei, SY andLai, CF and Chiang, WC and Schrimpf, C and Yang, KC and Lai, LC andChen, YM and Chu, TS and Lin, SL
The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury-induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during ren...

Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.
Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A
Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Ca...

Targeted bisulfite sequencing for biomarker discovery.
Morselli, M and Farrell, C and Rubbi, L and Fehling, HL and Henkhaus, Rand Pellegrini, M
Cytosine methylation is one of the best studied epigenetic modifications. In mammals, DNA methylation patterns vary among cells and is mainly found in the CpG context. DNA methylation is involved in important processes during development and differentiation and its dysregulation can lead to or is associated with dis...

Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.
Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J
Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict i...